Featured Research

from universities, journals, and other organizations

New window on Parkinson's disease: Metallic probe proves able to detect fibrils from misfolded proteins in real time

Date:
December 17, 2012
Source:
Rice University
Summary:
Scientists discover a new molecular probe to track aggregated fibroids inside living cells that cause Parkinson's disease.

Fibrallar deposits associated with Parkinson's disease light up when combined with a ruthenium-based probe developed at Rice University.
Credit: Martí Group/Rice University

Rice University scientists have discovered a new way to look inside living cells and see the insoluble fibrillar deposits associated with Parkinson's disease.

Related Articles


The combined talents of two Rice laboratories -- one that studies the misfolded proteins that cause neurodegenerative diseases and another that specializes in photoluminescent probes -- led to the spectroscopic technique that could become a valuable tool for scientists and pharmaceutical companies.

The research by the Rice labs of Angel Martí and Laura Segatori appeared online this month in the Journal of the American Chemical Society.

The researchers designed a molecular probe based on the metallic element ruthenium. Testing inside live neuroglioma cells, they found the probe binds with the misfolded alpha-synuclein proteins that clump together and form fibrils and disrupt the cell's functions. The ruthenium complex lit up when triggered by a laser -- but only when attached to the fibril, which allowed aggregation to be tracked using photoluminescence spectroscopy.

Researchers trying to understand molecular mechanisms of protein misfolding have had limited alternatives to monitor protein aggregation in cells, Martí said. A probe that can monitor the formation of aggregates should be of great value in the search for drugs that break up fibrils or prevent them from ever forming.

Two years ago, Martí, an assistant professor of chemistry and bioengineering, and Rice graduate student Nathan Cook revealed their metallic compounds that switch on like a light bulb when they attach to misfolded proteins; that study involved the beta amyloids that form plaques in the brains of Alzheimer's sufferers.

At about the same time, Cook approached Segatori, the T.N. Law Assistant Professor of Chemical and Biomolecular Engineering and assistant professor of biochemistry and cell biology, to ask if she would serve on his dissertation committee. They started talking about his work with Martí, and Segatori quickly saw the potential of a partnership.

Segatori has made important strides in the study of diseases caused by proteins that misfold and clump together. Alzheimer's, Parkinson's and Gaucher diseases are examples, all the result of genetic mutations or conditions that disrupt the way proteins fold and keep them from performing their functions.

"There are a few compounds you can use to detect the presence of these types of protein aggregates, but none of them have been reported to work in cells," Segatori said. "When you're thinking about developing a therapeutic strategy, you want to be able to detect the presence of fibril aggregates in living cells, or even in animals. It's been very nice to collaborate with someone with the expertise to do this."

"The connection between Parkinson's and Alzheimer's is natural, although they are very different diseases because Alzheimer's beta amyloid peptides are extracellular, while the onset of Parkinson's is associated with alpha-synuclein protein inside cells," Martí said. "We always thought we could apply the same techniques we used for beta amyloids to probe the aggregation of other proteins.

"When we learned that Laura has cells that overexpress alpha-synuclein, we thought, 'That's perfect.' She had the system and we had the probes," he said.

Segatori pointed out the ruthenium complex has no therapeutic benefit for Parkinson's sufferers, but "is a step toward understanding the chemistry, which obviously will help in the development of drugs."

They see the possibility that metallic complexes can be tailored to tag aggregates implicated in other degenerative diseases. "Metal complexes are like Legos, in the sense that you can attach whatever you want to them," Cook said.

As a proof of principle, the researchers created an in vitro cell model of Parkinson's disease and found their ruthenium complexes clearly labeled fibrillar alpha-synuclein proteins in cells.

"We can use it to test our strategies to prevent misfolding of proteins or to increase their degradation, so they will be eliminated," Segatori said. "It will be an easy tool to use for a lot of experiments."

Kiri Kilpatrick, a graduate student in Segatori's lab, co-authored the paper.

The National Science Foundation and the Welch Foundation supported the research.


Story Source:

The above story is based on materials provided by Rice University. The original article was written by Mike Williams. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nathan P. Cook, Kiri Kilpatrick, Laura Segatori, Angel A. Mart. Detection of α-Synuclein Amyloidogenic Aggregatesin Vitroand in Cells using Light-Switching Dipyridophenazine Ruthenium(II) Complexes. Journal of the American Chemical Society, 2012; 121214074651005 DOI: 10.1021/ja3100287

Cite This Page:

Rice University. "New window on Parkinson's disease: Metallic probe proves able to detect fibrils from misfolded proteins in real time." ScienceDaily. ScienceDaily, 17 December 2012. <www.sciencedaily.com/releases/2012/12/121217140633.htm>.
Rice University. (2012, December 17). New window on Parkinson's disease: Metallic probe proves able to detect fibrils from misfolded proteins in real time. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2012/12/121217140633.htm
Rice University. "New window on Parkinson's disease: Metallic probe proves able to detect fibrils from misfolded proteins in real time." ScienceDaily. www.sciencedaily.com/releases/2012/12/121217140633.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Matter & Energy News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Who Will Failed Nuclear Talks Hurt Most?

Who Will Failed Nuclear Talks Hurt Most?

Reuters - Business Video Online (Nov. 25, 2014) — With no immediate prospect of sanctions relief for Iran, and no solid progress in negotiations with the West over the country's nuclear programme, Ciara Lee asks why talks have still not produced results and what a resolution would mean for both parties. Video provided by Reuters
Powered by NewsLook.com
Flying Enthusiast Converts Real-Life Aircraft Cockpit Into Simulator

Flying Enthusiast Converts Real-Life Aircraft Cockpit Into Simulator

Reuters - Innovations Video Online (Nov. 25, 2014) — A virtual flying enthusiast converts parts of a written-off Airbus aircraft into a working flight simulator in his northern Slovenian home. Jim Drury reports. Video provided by Reuters
Powered by NewsLook.com
Car Park Solution for Flexible Green Energy

Car Park Solution for Flexible Green Energy

Reuters - Innovations Video Online (Nov. 24, 2014) — A British solar power start-up says that by covering millions of existing car park spaces around the UK with flexible solar panels, the country's power problems could be solved. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Microsoft Adds Robot Guards, Ushers In Sci-Fi Apocalypse

Microsoft Adds Robot Guards, Ushers In Sci-Fi Apocalypse

Newsy (Nov. 23, 2014) — Microsoft has robotic security guards working at its Silicon Valley Campus. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Space & Time

Matter & Energy

Computers & Math

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins